Chapter 45: Organization of the Nervous System, Basic Functions of Synapses, and Neurotransmitters

Written By: Razaullah Khattak (DPT Medical Professional)

Student Source Reference: Guyton and Hall Textbook of Medical Physiology

Chapter: 45

To read more check out Chapter 28:

https://mednotesbyrazaullah.blogspot.com/2026/09/chapter-28-urine-concentration-and.html

General Design of the Nervous System

The nervous system functions as an intricate communication and processing network designed to regulate human bodily activities. Operating through more than 100 billion neurons, the central nervous system collects environmental and internal stimuli via specialized sensory receptors, transfers this information along specific pathways, and integrates it to produce appropriate physiological or motor responses. Highly structured anatomical connections, including the somatosensory and skeletal motor axes, ensure that incoming inputs are organized systematically across multiple levels of the spinal cord, brainstem, subcortical structures, and cerebral cortex.

Information processing within the central nervous system relies heavily on specialized functional junctions known as synapses. By controlling signal transmission through chemical neurotransmitters or electrical channels, synapses filter irrelevant sensory data, route critical signals to specific motor and integrative centers, and store experiences as memories for future cognitive processing. Understanding the fundamental architecture of neurons, the mechanics of synaptic transmission, signal summation, and the factors influencing neuronal excitability provides the baseline framework for modern neurophysiology and clinical neurology.

Central Nervous System Neuron: The Basic Functional Unit

• Central nervous system contains over 100 billion neurons.
• Inputs enter via dendrites and the cell body.
• Neurons contain 200 to 200,000 synaptic connections.
• Output signal travels through a single axon.
• Axon branches extensively to target other areas.
• Synapses enforce one-way forward signal transmission.
• Forward transmission directs signals toward specific targets.

Sensory Part of the Nervous System Sensory Receptors

• Nervous system activities begin with sensory excitation.
• Sensory receptors include visual, auditory, and tactile types.
• Sensory experiences trigger immediate brain reactions.
• Sensory experiences store as long-term memories.
• Somatosensory axis transmits surface and deep signals.
• Nerves carry sensory input into spinal cord.
• Reticular substance receives incoming sensory signals.
• Cerebellum receives sensory inputs from peripheral nerves.
• Thalamus processes incoming peripheral sensory signals.
• Cerebral cortex receives structured somatosensory inputs.

Motor Part of the Nervous System Effectors

• Primary nervous role is controlling bodily activities.
• Controls contraction of skeletal muscles throughout body.
• Controls smooth muscle contraction in internal organs.
• Regulates chemical secretion from exocrine glands.
• Regulates active chemical secretion from endocrine glands.
• Muscles and glands act as anatomical effectors.
• Skeletal motor axis controls voluntary muscle movement.
• Autonomic nervous system controls internal organ systems.
• Spinal cord controls automatic muscle response centers.
• Medulla and pons regulate lower motor functions.
• Basal ganglia help control complex motor patterns.
• Cerebellum coordinates smooth execution of movements.
• Motor cortex directs deliberate muscle movement patterns.

Processing of Information Integrative” Function

• Brain processes incoming information for proper responses.
• Over 99 percent of sensory inputs are discarded.
• Irrelevant clothing contact and background noise are ignored.
• Important sensory inputs channel directly into motor regions.
• Integrative function directs signals to cause desired actions.
• Touch on hot stove causes immediate hand withdrawal.

Role of Synapses in Processing Information

• Synapse is the junction point between adjacent neurons.
• Synapses dictate exact direction of nerve signals.
• Facilitatory and inhibitory signals control synaptic transmission.
• Synapses can block weak incoming nerve signals.
• Synapses select, amplify, and channel nerve signals.

Storage of Information Memory

• Most sensory information is stored for future use.
• Cerebral cortex serves as main memory storage.
• Basal regions and spinal cord store small memories.
• Memory storage is a specialized synaptic function.
• Repeated signal passage increases synaptic transmission capability.
• Increased synaptic transmission capability is called facilitation.
• Facilitated synapses allow brain-generated thoughts to trigger memories.
• Thinking processes compare new inputs with stored memories.
• Memories help channel new information to motor areas.

Major Levels of Central Nervous System Function

Spinal Cord Level

• Spinal cord performs complex independent reflex functions.
• High neck spinal cord transection preserves local reflexes.
• Cord circuits execute complex walking movement patterns.
• Withdrawal reflexes pull body parts away from pain.
• Leg stiffening reflexes support body against gravity.
• Cord circuits control local blood vessel tone.
• Cord circuits regulate gastrointestinal and urinary movements.
• Higher brain centers command lower spinal cord centers.

Lower Brain or Subcortical Level

• Subconscious activities are controlled by lower brain areas.
• Medulla, pons, and mesencephalon govern lower functions.
• Hypothalamus, thalamus, and basal ganglia control subcortical tasks.
• Medulla and pons control arterial pressure and respiration.
• Cerebellum and reticular substance control body equilibrium.
• Subcortical areas control salivation and lip licking.
• Emotional patterns like anger occur without cerebral cortex.

Higher Brain or Cortical Level

• Cerebral cortex functions as a large memory storehouse.
• Cortex always operates together with lower brain centers.
• Cortical information converts imprecise lower functions to precise.
• Cortex is essential for most human thought processes.
• Lower brain centers trigger wakefulness in cerebral cortex.

Comparison of the Nervous System with a Computer

• Computers and nervous systems share structural functional features.
• Computer input circuits equal sensory nervous system parts.
• Computer output circuits equal motor nervous system parts.
• Simple computers operate similarly to simple spinal reflexes.
• Complex computer outputs rely on input and memory.
• Central processing unit directs operational sequence order.
• Central processing unit equals brain control mechanisms.
• Brain continuously computes daily bodily action courses.

Central Nervous System Synapses

• Information transmits as action potentials called nerve impulses.
• Synapses can block transmission of nerve impulses.
• Synapses convert single impulses into repetitive impulses.
• Synapses integrate impulses to form complex signal patterns.

Types of Synapses Chemical and Electrical

• Two main types are chemical and electrical synapses.
• Human central nervous system uses mostly chemical synapses.
• Presynaptic neuron secretes chemical neurotransmitter at synapse.
• Neurotransmitters act on postsynaptic membrane receptor proteins.
• Over 40 important transmitter substances have been discovered.
• Common transmitters include acetylcholine, norepinephrine, and GABA.
• Electrical synapses contain direct fluid channels called gap junctions.
• Gap junctions allow free movement of intracellular ions.
• Visceral smooth muscle uses gap junctions for transmission.
• Cardiac muscle cells transmit action potentials via gap junctions.

"One-Way" Conduction at Chemical Synapses

• Chemical synapses transmit signals in one direction only.
• Signal travels from presynaptic to postsynaptic neuron.
• Electrical synapses can transmit signals in both directions.
• One-way conduction allows signals to reach specific goals.

Physiologic Anatomy of the Synapse

• Anterior motor neuron consists of soma, axon, dendrites.
• Soma is main body of anterior motor neuron.
• Single axon extends from soma into peripheral nerve.
• Dendrites are branching projections extending into surrounding areas.
• Presynaptic terminals lie on dendrites and soma surfaces.
• About 80 to 95 percent lie on dendrites.
• Only 5 to 20 percent lie on soma.
• Terminals originate from many other incoming neurons.
• Excitatory presynaptic terminals secrete exciting neurotransmitter substances.
• Inhibitory presynaptic terminals secrete inhibiting neurotransmitter substances.
• Neurons vary by cell size, dendrite length, axon size.

Presynaptic Terminals

• Terminals resemble small round or oval end-feet knobs.
• Synaptic cleft separates presynaptic terminal from postsynaptic soma.
• Synaptic cleft width measures 200 to 300 angstroms.
• Presynaptic terminal contains transmitter vesicles and mitochondria.
• Transmitter vesicles store neurotransmitters that alter postsynaptic permeability.
• Mitochondria provide ATP energy for synthesizing new transmitters.
• Presynaptic depolarization causes transmitter vesicles to empty.

Role of Calcium Ions in Transmitter Release

• Presynaptic membrane contains voltage-gated calcium channels.
• Action potential depolarization opens presynaptic calcium channels.
• Calcium ions flow rapidly into presynaptic terminal.
• Transmitter release quantity relates directly to entering calcium.
• Calcium ions bind to internal release site protein molecules.
• Binding opens release sites to discharge transmitter vesicles.
• Acetylcholine vesicles contain 2000 to 10,000 molecules each.

Action of Transmitter on Postsynaptic Neuron

• Postsynaptic membrane contains large numbers of receptor proteins.
• Receptors feature extracellular binding component and ionophore component.
• Ionophore passes completely through postsynaptic cell membrane.
• Ionophore acts as ion channel or second messenger activator.

Ion Channels

• Postsynaptic ion channels are cation or anion channels.
• Cation channels allow passage of positive sodium ions.
• Anion channels allow passage of negative chloride ions.
• Cation channel negative charges attract positive sodium ions.
• Cation channel negative charges repel incoming chloride ions.
• Anion channels block passage of large hydrated cations.
• Opening cation channels excites the postsynaptic neuronal membrane.
• Opening anion channels inhibits the postsynaptic neuronal membrane.
• Transmitter-activated ion channels open and close within milliseconds.

"Second Messenger" System in Postsynaptic Neuron

• Prolonged neuronal changes require intracellular second messenger systems.
• G-protein complex attaches to intracellular receptor portion.
• G-protein consists of alpha, beta, and gamma components.
• Activation frees alpha component to move inside cytoplasm.
• Alpha component opens specific prolonged membrane ion channels.
• Alpha component activates cyclic AMP or cyclic GMP synthesis.
• Alpha component directly activates intracellular enzymatic pathways.
• Alpha component triggers gene transcription and protein synthesis.
• Gene transcription alters neuronal structure and long-term memory.

Excitatory or Inhibitory Receptors

• Postsynaptic activation causes neuronal excitation or inhibition.
• Dual receptor capability adds restraint dimension to control.

Excitation Mechanisms

• Opening sodium channels increases internal positive electrical potential.
• Depressing chloride or potassium channels raises membrane potential.
• Intracellular metabolic changes increase excitatory membrane receptor numbers.

Inhibition Mechanisms

• Opening chloride channels allows negative ions into cell.
• Increasing potassium conductance allows positive ions outward.
• Receptor enzyme activation depresses cell metabolic functions.
• Chemical Substances That Function as Synaptic Transmitters
• Over 50 chemical substances function as synaptic transmitters.
• Transmitters divide into small-molecule and neuropeptide groups.
• Small-molecule transmitters cause acute rapidly acting responses.
• Neuropeptides cause slowly acting, long-term neuronal actions.

Small-Molecule, Rapidly Acting Transmitters

• Synthesized in cytosol of presynaptic nerve terminal.
• Active transport absorbs transmitters into presynaptic vesicles.
• Action potential causes millisecond release of transmitter vesicles.
• Postsynaptic response occurs within a millisecond or less.
• Vesicle membrane invaginates to recycle within presynaptic terminal.
• Choline acetyltransferase synthesizes acetylcholine from acetyl-CoA and choline.
• Cholinesterase splits acetylcholine rapidly inside synaptic cleft.
• Choline actively transports back into presynaptic terminal.

Characteristics of Small-Molecule Transmitters

• Acetylcholine is secreted by motor cortex pyramidal terminals.
• Acetylcholine is secreted by motor neurons innervating skeletal muscles.
• Acetylcholine is secreted by autonomic preganglionic neurons.
• Acetylcholine is secreted by parasympathetic postganglionic neurons.
• Norepinephrine is secreted by locus ceruleus neurons.
• Norepinephrine controls overall mental activity and wakefulness levels.
• Dopamine is secreted by substantia nigra neurons.
• Dopamine termination occurs mainly in basal ganglia striatum.
• Dopamine acts primarily as an inhibitory neurotransmitter.
• Glycine is secreted mainly at spinal cord synapses.
• Glycine always acts as an inhibitory transmitter substance.
• GABA is secreted in spinal cord, cerebellum, cortical areas.
• GABA always causes postsynaptic neuronal inhibition.
• Glutamate is secreted in central sensory input pathways.
• Glutamate always causes postsynaptic excitation.
• Serotonin is secreted by median raphe brainstem nuclei.
• Serotonin acts as an inhibitor of cord pain pathways.
• Nitric oxide synthesizes instantly as needed without storage.
• Nitric oxide diffuses out over seconds to nearby neurons.
• Nitric oxide alters postsynaptic metabolic functions modifying excitability.

Neuropeptides

• Neuropeptides are synthesized by ribosomes in cell body.
• Endoplasmic reticulum and Golgi apparatus process neuropeptide precursors.
• Golgi packages neuropeptides into transmitter vesicles for cytoplasm.
• Axonal streaming transports vesicles at centimeters per day.
• Neuropeptide vesicles undergo autolysis and are not reused.
• Neuropeptides release in much smaller quantities than small-molecules.
• Neuropeptides are thousandfold more potent than small-molecule transmitters.
• Neuropeptides cause prolonged closure of specific ion channels.
• Neuropeptides induce long-term changes in cellular gene activation.

Electrical Events During Neuronal Excitation

• Resting Membrane Potential of Neuronal Soma
• Spinal motor neuron resting membrane potential is −65 millivolts.
• Lower voltage allows positive and negative excitability control.
• Decreasing negativity makes neuronal membrane far more excitable.
• Increasing negativity makes neuronal membrane far less excitable.

Ion Concentration Differences Across Somal Membrane

• Extracellular sodium concentration measures high at 142 mEq/L.
• Intracellular sodium concentration measures low at 14 mEq/L.
• Strong membrane sodium pump transports sodium outward continuously.
• Intracellular potassium concentration measures high at 120 mEq/L.
• Extracellular potassium concentration measures low at 4.5 mEq/L.
• Potassium pump transports potassium ions into cell interior.
• Extracellular chloride concentration measures high at 107 mEq/L.
• Intracellular chloride concentration measures low at 8 mEq/L.
• Negative −65 millivolt charge repels internal chloride outward.
• Nernst potential opposes net movement of specific ions.
• Calculated Nernst potential for sodium equals +61 millivolts.
• Calculated Nernst potential for potassium equals −86 millivolts.
• Calculated Nernst potential for chloride equals −70 millivolts.

Uniform Distribution of Electrical Potential Inside Soma

• Intracellular somal fluid contains highly conductive electrolytic solution.
• Large somal diameter offers low resistance to current flow.
• Potential change anywhere in soma spreads equally throughout interior.
• Equal potential spread enables summation of incoming inputs.

Effect of Synaptic Excitation Excitatory Postsynaptic Potential

• Excitatory transmitter increases membrane permeability to sodium ions.
• Rapid sodium influx neutralizes internal somal membrane negativity.
• Membrane potential rises from −65 toward −45 millivolts.
• Positive shift in voltage represents excitatory postsynaptic potential.
• Single presynaptic discharge cannot cause an EPSP alone.
• Simultaneous discharge of 40 to 80 terminals causes excitation.

Generation of Action Potentials in Initial Axon Segment

• Action potential begins in axon initial segment region.
• Soma contains very few voltage-gated sodium channels.
• Axon initial segment contains sevenfold higher sodium channel concentration.
• Axon initial segment threshold requires +10 to +20 millivolts EPSP.
• Action potential travels peripherally along axon and backward.

Electrical Events During Neuronal Inhibition

• Effect of Inhibitory Synapses Inhibitory Postsynaptic Potential
• Inhibitory synapses open postsynaptic membrane chloride channels.
• Chloride influx moves membrane potential toward −70 millivolts.
• Potassium channel opening allows positive ions to diffuse outward.
• Hyperpolarization increases internal negativity beyond normal resting levels.
• Increased internal negativity represents an inhibitory postsynaptic potential.
• IPSP of −5 millivolts inhibits signal transmission through synapse.

Presynaptic Inhibition

• Presynaptic inhibition occurs before signal reaches postsynaptic membrane.
• Inhibitory transmitter GABA releases onto presynaptic nerve fibrils.
• GABA opens anion channels for chloride influx into terminal.
• Negative chloride ions cancel incoming sodium action potential effects.
• Presynaptic inhibition minimizes lateral signal spread in sensory pathways.

Time Course of Postsynaptic Potentials

• Excitatory transmitter increases sodium permeability for 1 to 2 milliseconds.
• EPSP slowly declines over the subsequent 15 milliseconds.
• Excess positive charges leak outward to restore resting potential.
• Inhibitory transmitter increases potassium or chloride permeability for 1 to 2 milliseconds.
• IPSP dies away slowly over approximately 15 milliseconds.
• Neuropeptide transmitters excite or inhibit for minutes or hours.

Summation and Facilitation in Neurons

Spatial Summation in Neurons Threshold for Firing

• Single terminal discharge releases transmitter causing 0.5 to 1 millivolt EPSP.
• Multiple terminals firing simultaneously add potentials together.
• High somal electrical conductivity allows simultaneous potential addition.
• Summation of widely spaced terminal potentials is spatial summation.
• Action potential develops once summated EPSP reaches threshold.

Temporal Summation

• Synaptic membrane channels close within 1 millisecond.
• Postsynaptic potential changes persist for up to 15 milliseconds.
• Successive rapid discharges from one terminal summate together.
• Rapid discharge rate increases summated postsynaptic potential level.

Simultaneous Summation of EPSP and IPSP

• EPSP and IPSP forces nullify each other simultaneously.
• Inhibitory signals can turn off active excitatory neuronal responses.

Facilitation of Neurons

• Summated postsynaptic potential approaching threshold facilitates neuron.
• Facilitated neuron membrane potential sits nearer firing threshold.
• Subsequent weak incoming signals easily trigger facilitated neuron firing.
• Special Functions of Dendrites
• Dendrites extend 500 to 1000 micrometers around soma.
• Dendrites receive inputs across large spatial surrounding areas.
• 80 to 95 percent of presynaptic terminals terminate on dendrites.
• Most dendrites cannot transmit self-propagating action potentials.
• Dendrites contain low voltage-gated sodium channel concentrations.
• Signals travel down dendrites via electrotonic current conduction.
• Membrane leakage causes decremental conduction toward cell soma.
• Farther synaptic distances cause greater potential signal decrements.
• Synapses near soma exert stronger effects on excitation.
• Dendrites summate incoming excitatory and inhibitory potentials simultaneously.
• Axon hillock inhibitory synapses block action potential generation directly.
• State of Excitation and Rate of Firing.
• Excitatory state means summated excitation exceeds inhibition degree.

Disclaimer: This content is for educational purposes only and not a substitute for professional medical advice.